Prognostic Implications of Isolated Tumor Cells and Micrometastases in Sentinel Nodes of Patients with Invasive Breast Cancer: 10-Year Analysis of Patients Enrolled in the Prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study
ABSTRACT Sentinel lymph node biopsy (SLNB) is a more sensitive and accurate nodal staging procedure than axillary lymph node dissection (ALND). Because of increased pathologic evaluation in the sentinel node era, more nodal micrometastases (MIC) (> 0.2 mm to 2 mm) and isolated tumor cells (ITC; < or = 0.2 mm) have been identified. We present the 10-year analysis of our prospective SLN study, focusing on regional axillary node status and distant metastases in patients with nodal ITC and MIC.
From 1996 to 2005, breast cancer patients were enrolled in an Institutional Review Board-approved, multicenter study. SLNs were examined at multiple levels by hematoxylin and eosin; most (85%) hematoxylin and eosin-negative SLNs were also examined by cytokeratin immunohistochemistry. Data from 1,259 patients with invasive breast cancer and in whom an SLN was found were reviewed for this analysis.
Of the 1,259 patients, 893 (71%) had negative SLNs, 25 (2%) had ITCs, 57 (5%) had MIC, and 284 (23%) had positive SLNs. None of the 13 patients with ITCs who underwent an ALND had additional positive nodes, compared with 27% (11 of 41) of patients with MIC. At a mean followup of 4.9 years, the distant recurrence rates for SLN-negative, ITC, MIC, and SLN-positive groups were 6%, 8%, 14%, and 21%, respectively. The presence of MIC in the SLN was associated with a significantly shorter disease-free interval than was SLN negativity (p < 0.02 by Cox regression model).
This prospective breast cancer study found that sentinel node MIC, but not ITCs, were associated with additional positive nodes and with distant recurrence. These data suggest that ALND may be unnecessary in patients with ITCs. But ALND and more aggressive adjuvant therapy should be considered in patients with SLN micrometastases.
- SourceAvailable from: Earle Holmes
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- "The dimension of tumor involvement in positive LNs has been distinguished in stages N0 and N1 as isolated tumor cells, tumor clusters, and micrometastasis by AJCC LN staging system . Survival analyses of the breast cancer patients with isolated tumor cells and micrometastasis in the sentinel lymph nodes showed controversial results      . There is no further distinction of tumor dimension above 2 mm in the LNs, whereas only the metLN is taken into account. "
ABSTRACT: The number of positive axillary lymph nodes (LNs) is the only node-related factor for prognostic evaluation of breast cancer recognized by AJCC (TNM staging). However, N staging may not completely reflect LN tumor involvement due to the erroneous count of LNs in the presence of matted LNs and different tumor volume in LNs. Additionally, the positive/total LN ratio (LNR) has been shown to outperform N staging in survival prediction. In our study, to better quantify the tumor involvement of axillary LNs, we measured the cross-sectional cancer area (CSCA) of the positive LNs in 292 breast cancer patients diagnosed between 1998 and 2000 in our institution and compared its prognostic value to that of number of positive LNs (metLN)/N stage and LNR. Statistical analyses of these three LN-related factors were performed by Kaplan-Meier method and multivariate Cox's regression model. Patients were divided into three groups based on the different LN CSCA (<50, 50-500, and >500 mm(2)), or LNR (<0.1, 0.1-0.65, and >0.65), or N stage (N1-N3). Multivariate analysis demonstrated LNR was the most significant LN-related survival predictor with hazard ratio (HR) 25.0 (P = 0.001), compared to the metLN (HR 0.09, P = 0.052) and CSCA (HR 2.24, P = 0.323).10/2012; 2012:161964. DOI:10.1155/2012/161964
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ABSTRACT: Step-sectioning and anti-cytokeratin immunohistochemistry allow detection of micrometastases and nanometastases down to the single cell level, but they are labor intensive and time consuming. Reverse-transcription polymerase chain reaction can be performed efficiently, but it cannot currently detect less than several thousand cancer cells per lymph node. Improvements in molecular assays are thus required for reliable use in clinical settings. Whole-axilla dissection maximizes chances of detecting micrometastases and nanometastases. However, sentinel lymph node analysis provides an important fraction of this information in more convenient surgical and laboratory settings. Nanometastases have been shown to be a risk factor for event-free survival and for metastatic relapse. Thus, a re-evaluation of current TNM staging procedures appears needed. Corresponding therapeutic strategies should be tested accordingly in prospective clinical trials with adequate follow-up time. Microinvasion of the bone marrow is an independent prognostic indicator for disease recurrence and death from cancer, but bone marrow analyses are poorly suited to monitor disease course and response to therapy. The detection of circulating tumor cells has been shown to provide useful prognostic information, but it correlates poorly with bone marrow microinvasion, and the latter remains an independent, albeit hard to manage, prognostic determinant. KeywordsBreast cancer-Metastasis-Lymph nodes-Bone marrow-Prognosis-MarkersCurrent Breast Cancer Reports 06/2010; 2(2):96-106. DOI:10.1007/s12609-010-0013-5
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ABSTRACT: Although the current American Joint Commission on Cancer (AJCC) staging system is the most widely used classification scheme for the prognostication of breast cancer, recent work has offered the potential for refinement of this system. Incorporation of grade, lymphovascular invasion, and various biomarkers have all been proposed as options for improvement of primary tumor staging. In addition, there remains controversy regarding optimal staging of lymph node metastases, as the value isolated tumor cells and micrometastases, lymph node ratio, and the value of internal mammary nodes remain at issue. Finally, nuances about the location and number of distant metastases, and the amount of circulating tumor cells may differentiate patients within Stage IV disease. This review highlights recent advances in breast cancer research that may offer insight into potential ways that the AJCC staging system can be improved.Current Breast Cancer Reports 06/2011; 3(2). DOI:10.1007/s12609-011-0041-9